Cost associated with a relapse-free patient in multiple sclerosis: A real-world health indicator.

BACKGROUND: The efficacy and safety of disease-modifying therapies (DMTs) in multiple sclerosis (MS) are well known; however, owing to their high costs, determining real-world outcomes is essential to evaluate the cost-effectiveness of different therapeutic strategies. This study aimed to investigate the variability in the annual cost of DMTs associated with a relapse-free patient in a representative population cohort of relapsing-remitting MS (RRMS), and whether this could serve as an appropriate health indicator. METHODS: We analyzed the patients followed up in our MS clinic during the years 2016 and 2019, and selected patients belonging to our health district diagnosed with RRMS. The treatment cost associated with a relapse-free patient was the ratio between the total cost of DMTs and the number of relapse-free patients, treated and not treated, during the year of the study. RESULTS: A total of 158 patients with RRMS in 2016 and 183 in 2019 were included in our study. In 2016, 101 patients with RRMS (63.9%) received treatment with DMTs and 120 patients (75.9%) remained relapse-free. The mean cost of DMTs per patient in 2016 was €7414.3 (95% confidence interval [CI]: 6325.2-8503.4) considering all the patients (treated and not treated). In 2019, 126 patients (68.9%) received DMTs and 151 patients (82.5%) remained relapse-free. The mean cost of DMTs per patient in 2019 was €6985.4 (95% CI: 5986.9-7983.9) considering all the patients. The cost per year of DMTs to achieve a relapse-free patient was €9762.2 in 2016 and €8465.8 in 2019. CONCLUSIONS: The treatment cost per year to achieve a relapse-free patient was stable during successive measurements in the same population. Therefore, it may be considered a good real-world health indicator for patients with RRMS treated with DMTs.

A multicriteria decision analysis (MCDA) applied to three long-term prophylactic treatments for hereditary angioedema in Spain.

Introduction: Hereditary angioedema (HAE) is a rare genetic disease that impairs quality of life and could be life-threatening. The aim of this study was to apply a multicriteria decision analysis to assess the value of three long-term prophylactic (LTP) therapies for HAE in Spain. Methods: A multidisciplinary committee of 10 experts assessed the value of lanadelumab (subcutaneous use), C1-inhibitor (C1-INH; intravenous), and danazol (orally), using placebo as comparator. We followed the EVIDEM methodology that considers a set of 13 quantitative criteria. The overall estimated value of each intervention was obtained combining the weighting of each criterion with the scoring of each intervention in each criterion. We used two alternative weighting methods: hierarchical point allocation (HPA) and direct rating scale (DRS). A reevaluation of weightings and scores was performed. Results: Lanadelumab obtained higher mean scores than C1-INH and danazol in all criteria, except for the cost of the intervention and clinical practice guidelines. Under the HPA method, the estimated values were 0.51 (95% confidence interval [CI]: 0.44-0.58) for lanadelumab, 0.47 (95%CI: 0.41-0.53) for C1-INH, and 0.31 (95%CI: 0.24-0.39) for danazol. Similar results were obtained with the DRS method: 0.51 (95%CI: 0.42-0.60), 0.47 (95%CI: 0.40-0.54), and 0.27 (95%CI: 0.18-0.37), respectively. The comparative cost of the intervention was the only criterion that contributed negatively to the values of lanadelumab and C1-INH. For danazol, four criteria contributed negatively, mainly comparative safety. Conclusion: Lanadelumab was assessed as a high-value intervention, better than C1-INH and substantially better than danazol for LTP treatment of HAE.

Beneficial effect of corticosteroids in preventing mortality in patients receiving tocilizumab to treat severe COVID-19 illness.

OBJECTIVES: To assess the characteristics and risk factors for mortality in patients with severe coronavirus disease-2019 (COVID-19) treated with tocilizumab (TCZ), alone or in combination with corticosteroids (CS). METHODS: From March 17 to April 7, 2020, a real-world observational retrospective analysis of consecutive hospitalized adult patients receiving TCZ to treat severe COVID-19 was conducted at our 750-bed university hospital. The main outcome was all-cause in-hospital mortality. RESULTS: A total of 1,092 patients with COVID-19 were admitted during the study period. Of them, 186 (17%) were treated with TCZ, of which 129 (87.8%) in combination with CS. Of the total 186 patients, 155 (83.3 %) patients were receiving noninvasive ventilation when TCZ was initiated. Mean time from symptoms onset and hospital admission to TCZ use was 12 (±4.3) and 4.3 days (±3.4), respectively. Overall, 147 (79%) survived and 39 (21%) died. By multivariate analysis, mortality was associated with older age (HR = 1.09, p < 0.001), chronic heart failure (HR = 4.4, p = 0.003), and chronic liver disease (HR = 4.69, p = 0.004). The use of CS, in combination with TCZ, was identified as a protective factor against mortality (HR = 0.26, p < 0.001) in such severe COVID-19 patients receiving TCZ. No serious superinfections were observed after a 30-day follow-up. CONCLUSIONS: In patients with severe COVID-19 receiving TCZ due to systemic host-immune inflammatory response syndrome, the use of CS in addition to TCZ therapy, showed a beneficial effect in preventing in-hospital mortality.

Outpatient treatment of Pseudomonas aeruginosa bronchial colonization with long-term inhaled colistin, tobramycin, or both in adults without cystic fibrosis.

STUDY OBJECTIVE: To compare clinical and microbiologic outcomes in adults without cystic fibrosis who had Pseudomonas aeruginosa bronchial colonization and were receiving inhaled colistin or colistin plus tobramycin with those who were receiving inhaled tobramycin as outpatient treatment. DESIGN: Prospective, observational cohort study. SETTING: Referral pneumology service at a tertiary university care hospital. PATIENTS: Eighty-one Caucasian adults without cystic fibrosis who received 97 courses of inhaled colistin alone, colistin plus tobramycin, or inhaled tobramycin alone as outpatient treatment of P. aeruginosa bronchial colonization between January 2004 and December 2008. MEASUREMENTS AND MAIN RESULTS: The frequency and duration of hospitalizations for respiratory exacerbations were the primary outcomes compared among treatment groups. Secondary outcomes were emergence of bacterial resistance, antibiotic use during admission, emergence of other opportunistic microorganisms, achievement of sustained P. aeruginosa eradication in the airways, and mortality, as well as safety and changes in respiratory function. No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, adverse events, mortality, or emergence of other opportunistic microorganisms. Emergence of resistance to colistin was lower than resistance to tobramycin (hazard ratio 0.09, 95% confidence interval [CI] 0.03-0.32). Patients treated with both inhaled antibiotics had fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone (relative risk [RR] 0.33, 95% CI 0.10-1.12, and RR 0.27, 95% CI 0.08-0.93, respectively). CONCLUSION: Results with colistin were similar to those with tobramycin for inhaled treatment of P. aeruginosa colonization in this population; however, combined use of colistin and tobramycin appeared to be associated with fewer days of hospitalization and shorter duration of antibiotic treatment. Prospective, double-blind, placebo-controlled trials of outpatient nebulized antibiotics, especially colistin plus tobramycin, should be performed to ascertain the efficacy of this therapy for treatment of P. aeruginosa colonization in patients without cystic fibrosis.

Changes in biochemical, hematological and immunological profiles after low-dose intravenous immunoglobulin administration in patients with hypogammaglobulinemia.

We assessed the immediate effect of intravenous immunoglobulins (IVIG) on the biochemical, immunological and hematological profiles in patients with hypogammaglobulinemia. Over a period of three months, patients with antibody deficiencies, who had been established on stable IVIG treatment as replacement therapy in our hospital, were enrolled in the study. Participants underwent pre-therapy determinations of their biochemical, immunological and hematological profiles. Laboratory determinations were repeated after completion of IVIG infusions. Over the study period, fourteen patients were enrolled and a total of 34 pre- and post-IVIG infusion determinations were performed and results compared. We found that low-dose IVIG treatment in patients with hypogammaglobulinemia results in post-infusion biochemical and hematological changes, as follows: an increase in total protein concentration and a reduction in albumin, total cholesterol, sodium and alkaline phosphatase concentrations as well as lymphocyte and platelet counts. All these biochemical and cellular changes seems to be transient, since they were not observed in the subsequent pre-infusion determination. However, in other patient populations, some of these changes might differ, depending on the dose of IVIG administered and the baseline condition and immunological status of the patient.